Thursday, November 14, 2013

"Olson and his team were able to identify a small protein, or peptide, in the scorpion's venom and use it to produce Tumor Paint. They grew a brain tumor on a mouse's back and injected the "paint" into a tail vein; within an hour, the cancer was lighting up. Tumor Paint was 500 times more sensitive than an MRI, and it didn't just work for brain cancer but breast, skin, prostate and colon cancers."

" IBM and MD Anderson announced the development of a prototype of a platform designed to provide treatment recommendations for and help guide the management of oncology patients."

"By identifying and weighing data-driven connections between the attributes in a patient’s profile and the knowledge corpus of published medical literature and guidelines in Watson, MD Anderson’s OncologyExpert Advisor can provide evidence-based treatment and management options that are personalized to that patient, to aid the physician’s treatment and care decisions."

FDA-approved antidepressant may combat deadly form of lung cancer, study finds - Office of Communications & Public Affairs - Stanford University School of Medicine: Excerpts:"...The phase-2 trial is now recruiting participants with small-cell lung cancer and other, similar conditions like aggressive gastrointestinal neuroendocrine cancers. The “repositioning” of an existing drug to treat a disorder other than the one for which it was originally approved is an example of how extremely large genetic and biological databases are changing the face of medicine.""...Specifically, the drugs activated a cellular self-destruct pathway that killed the cancer cells.""...The pipeline works by scanning the hundreds of thousands of gene-expression profiles (gathered by multiple researchers and stored in large databases) across many different cell types and tissues — some normal and some diseased, some treated with medications and some not. Alone, these profiles may not mean much to any one investigator or group, but when viewed together, researchers can pick out previously unsuspected patterns and trends.""Jahchan tested the effect of a tricyclic antidepressant called imipramine on human small-cell lung cancer cells grown in the laboratory and growing as tumors in laboratory mice. She found that the drug was able to potently activate a self-destruction pathway in the cancer cells and to slow or block metastases in the animals. The drug maintained its effectiveness regardless of whether the cancer cells had previously been exposed, and become resistant, to traditional chemotherapy treatments. Another drug, an antihistamine called promethazine, identified by the bioinformatics screen, also exhibited cancer-cell-killing abilities.""Further investigation showed that the drugs appear to work through a class of molecule on the cancer cells’ surfaces called G-protein-coupled receptors, but the researchers are continuing to investigate exactly how the drugs specifically kill neuroendocrine cancer cells."See more at: http://med.stanford.edu/ism/2013/september/antidepressant.html#sthash.OzJhnFka.dpufLink to full article here.

"A chemical commonly used as a preservative in dog food prevented the development of peripheral neuropathy associated with treatment with paclitaxel (Taxol) in a mouse model.

The majority of patients given paclitaxel for malignancies such as breast cancer experience painful neuropathy, which can be dose-limiting and can seriously impair quality of life. So a group of researchers from Johns Hopkins led by Ahmet Hoke, MD, PhD, screened some 2,000 compounds for neuroprotective effects in various cell lines.

They identified the antioxidant ethoxyquin -- approved by the FDA for use in animal feed 50 years ago -- as having the most pronounced effects. When they co-administered ethoxyquin with paclitaxel in mice, the intraepidermal nerve fiber damage that predictably occurs in the animals' paws didn't develop.

Hoke's team then were able to identify heat shock protein 90 as the molecule that mediated the neuroprotection through its effects on the levels of two proteins known as ATXN2 and SF3B2.

These findings suggest that ethoxyquin and its derivatives might be suitable for development to help prevent chemotherapy-induced nerve damage in the clinical setting, the researchers suggested in the Annals of Neurology."

"From targeted cancer drugs to molecular diagnostics, advances in genome sequencing are driving precision medicine. It’s defined by Pfizer as “an approach to discovering and developing medicines and vaccines that deliver superior outcomes for patients, by integrating clinical and molecular information to understand the basis of disease.”

Some use precision medicine synonymously with personalized medicine. Others say it’s a better term that captures the idea of personalized medicine more clearly: Not as medical care that’s tailored to an individual but rather the ability to classify individuals into smaller populations that might be more susceptible to certain diseases or respond to drugs differently. This term has been slowly gaining steam since 2011."

Friday, May 17, 2013

Crystal structure of the c-abl kinase domain (green) in complex with Sti-571 (imatinib, red). Rendered with Accelrys DS Visualizer Pro 1.6 and edited in the GIMP. Conformation and style made to match Image:Bcr abl sti.jpg, originally created by Mxpule for use in Wikipedia. (Photo credit: Wikipedia)

Berman and colleagues enrolled 28 patients with either CML or GIST, and prospectively analyzed levels of osteocalcin and serum N-telopeptide of type 1 collagen(Drug information on collagen) (NTX), a marker of bone resorption. Patients were on imatinib for a median of 31 months at baseline. Nineteen patients completed measures of bone mineral density at baseline, 1 year, and 2 years.

Ninety-five percent of the patients were found to have low levels of osteocalcin, and 37% of patients had no measurable amounts at least once during the study period.

Eleven patients (58%) had normal NTX levels. Only four patients (21%) had elevated levels of NTX, and four patients had low levels of NTX.

At 2 years, DEXA scans indicated that 47% of patients had a decrease in bone mineral density and 32% had no change. Seven of the nine patients with decreases saw significant changes at the total hip.

“Imatinib appears to halt or at least decrease bone growth,” Berman said. “Bone is always growing or remodeling. It slows when you are older, in postmenopausal women particularly, but it is always a living organ.”

***Of course, current practice is to give imatinib indefinitely. The authors, then, suggest careful monitoring of bone density and should the patient have indication of loss, consider therapy with calcium and vitamin D. They stated hormone therapy may need to be started. The role of bisphosphonates will also have to be later established.

Friday, April 26, 2013

Cancer is a disease that invokes fear, so it is not surprising that the public is eager to identify ways to decrease the risk. The media often features information on “Miracle Foods” and publicizes whether these foods can actually decrease the risk of cancer.

"Nutritional scientists and epidemiologists should be cognizant of the public health messages that are taken away from their individual studies and not sensationalize the findings or contribute to the media frenzy around a single study," the authors believe.

The authors mention two separate studies that theorize a decreased risk of ovarian cancer due to flavonoids in red onions and omega-3 in sea bass. Both of these studies were reported as fact on a popular television talk show. The authors assert that with further research, three other studies would have been found that can disprove the findings reported as true.

"The public needs more information about the effect of diet as a whole on cancer risk, as well as the importance of achieving and maintaining an ideal body weight, regular physical activity, and avoiding a sedentary lifestyle," the authors wrote.

Abstract:

"A recent episode of the Dr. Oz Show suggested endive, red onion, and sea bass as foods that can decrease the risk of ovarian cancer by up to 75%. However, the scientific evidence supporting these recommendations is limited. This commentary discusses some of the concerns related to the promotion of “miracle foods” by the media. Nutritional scientists and epidemiologists should be cognizant of the public health messages that are taken from their individual studies and not sensationalize the findings of a single study."

About Nutrition and Cancer: An International JournalNutrition and Cancer: An International Journal reports on current research and findings relative to the effects of nutrition on the etiology, therapy, and the prevention of cancer. The Journal presents original papers by experts around the world.

Tuesday, April 16, 2013

"The moment we find a useful biomarker, our ability to manage a condition improves: we treat diabetes by following the glycemic index, we treat HIV by following a viral load and a CD4 count. Conditions without biomarkers often frustrate treatment – after all, like the business adage – “you can’t manage what you don’t measure.” Although some diseases fall into this category, frustratingly, so does the symptom of pain. This week’s NEJM reports on a biomarker – specifically a neurologic signature through the use of functional MRI – with the hope that a method to objectively measure pain will allow for titration of medications to achieve effective symptomatic relief in the distressed patient."

Friday, April 12, 2013

LONDON, UK (GlobalData*), 10 April 2013 - Guidelines for off-label drug use hold immense commercial implications, and stricter controls are needed on medical compendia, given their influence in this field, states recent analysis by research and consulting firm GlobalData.

In all areas of healthcare, the line between the interests of regulators, insurers, physicians, and patients can be murky, and widespread off-label drug prescribing represents a growing grey area in oncology. This practice came under scrutiny by Rena Conti at the University of Chicago, in a recent study which shines a light on drugs that come with a hefty price tag, and are commended for numerous off-label uses despite uncertain clinical risks and benefits.

Medical compendia are meant to ensure that patients have access to the newest registered drugs when evidence emerges to support specific off-label indications, but their decisions can sometimes draw questions. A recent study lead by Conti establishes a benchmark for off-label use of certain expensive drugs with known safety issues, on the basis of guidance from privately published compendia. Insurers routinely rely on guidelines such as the National Comprehensive Cancer Network’s (NCCN) Drugs and Biologics Compendium to make coverage decisions for off-label indications, and Conti’s group found that from the US$12 billion spent on 10 leading chemotherapies in 2010, US$4.5 billion was spent off-label, and US$2 billion was spent on NCCN-supported uses.

Anita Angelica Moore, GlobalData’s Healthcare Analyst for Oncology, explains: “Advocates of medical compendia argue that off-label prescribing represents a crucial element in the oncology market, due to limited treatment options and the impracticability of FDA applications being submitted for every combination of agent and cancer type. However, critics contend that compendia publishers are too quick to recommend drugs based on limited research, and cite the possibility of conflicts of interest, especially in cases where compendia panel members are financially linked to drug manufacturers.

“Compendium guidelines play a large role in influencing prescribing patterns, and so their commercial implications are immense”, states Moore. “2011 saw the US’s largest payer Medicare base its reimbursement policy concerning the off-label use of Avastin for metastatic breast cancer on the NCCN compendia’s vote. That year, the US Food and Drug Administration (FDA) announced that Avastin, while still approved for other cancers, caused more harm than benefit in breast cancer patients. In a controversial decision, Medicare continued coverage for the off-label use of Avastin at a hefty annual price tag of US$88,000, a decision based largely on NCCN recommendations. Critics of this decision cite the fact that a third of the NCCN’s guideline-writing committee had financial ties to Avastin’s producers, Roche and Genentech.”

Conti also charted the prevalence and cost of off-label prescribing of 10 patent-protected, intravenous cancer drugs in 2010, and showed that Avastin was both more commonly used off than on label, and was the single largest contributor to off-label prescribing costs during that year.

Moore argues that such compendia are not the best judge, however: “Systematic analysis of major compendia has found a host of methodological problems, wide variety in recommendations, and a general lack of transparency. For instance, endorsements were given for Avastin in the 2010 NCCN compendia for adjuvant use in colorectal cancer, despite the drug having continually failed to improve outcomes when used in this capacity, and a negative study having been presented a full year earlier. This recommendation has since been updated, but the error showcases the failure of NCCN guidelines to update material.”

Thursday, April 11, 2013

"We believe that we should work to be happy, but could that be backwards? In this fast-moving and entertaining talk, psychologist Shawn Achor argues that actually happiness inspires productivity. (Filmed at TEDxBloomington.)

Shawn Achor is the CEO of Good Think Inc., where he researches and teaches about positive psychology."

Ontario did it first. Alberta followed suit, outdoing Ontario. Reducing generic drug reimbursement prices. Government paid advertisements (how much is that costing taxpayers? Actually just found out - $400,000!) would have you believe this is saving Alberta over $90 million big ones. The ramifications will be much more severe, more than what the government will let you know, maybe more than they fathomed.

"Beginning May 1, the Alberta government will force generic drug manufacturers to sell their products at 18 per cent of the price brand name drugs are sold at, compared with the current 35 per cent.

Hypothetically, if a bottle of Druggin costs $100, its generic equivalent Drugsler must be sold at $18, decreasing the generic drug manufacturer’s profit by $17 per bottle.

As profits decrease, the large generic drug manufacturers will react in two ways.

First, they will reduce or eliminate the rebates they pay to pharmacies for using their products. Pharmacies will, in turn, be forced to reduce their hours and their staff, even though the demand for pharmacists’ services will increase as baby boomers grow old and require more medication.

Second, generic drug manufacturers will reduce the supply of generic medications in Alberta."

"In his discussion, Gunter von Minckwitz, MD, PhD, of the German Breast Group and the University of Frankfurt, Germany, said there is increasing evidence that lapatinib is not as active as trastuzumab in a number of breast cancer therapy settings, perhaps because of the rapid development of secondary resistance and because dual blockade appears to be the most promising approach for the future."

It often takes time, but Health Canada has now made notice of updated prescribing information.Excerpt from Health Canada update via GlaxoSmithKline Inc:"Subject: Updated Information on Efficacy - TYKERB® (lapatinib ditosylate)-based regimens are less effective than HERCEPTIN®(trastuzumab)-based regimens in certain settings:

Based on the results of preplanned interim analyses of two studies, GlaxoSmithKline would like to advise you of the following:

In patients with HER2+ metastatic breast cancer who have not received prior trastuzumab, comparative data have shown that lapatinib-based regimens are less effective than trastuzumab based treatment regimens.

Prescribers are reminded that TYKERB® should not be prescribed in combination with capecitabine unless patients have progressed on prior trastuzumab therapy in the metastatic setting.

GlaxoSmithKline has updated the TYKERB® Product Monograph to include a statement that lapatinib-based regimens are less effective than trastuzumab-based regimens in certain settings.

CEREBEL(EGF111438) (N=540) is a randomised Phase III study comparing the effect of lapatinib in combination with capecitabine relative to trastuzumab in combination with capecitabine on the incidence of CNS as site of first relapse in women with HER2 positive metastatic breast cancer. Patients were stratified based on prior trastuzumab treatment (yes versus no) and number of prior treatments for metastatic disease (0 versus ≥1 line). The study was stopped early due to results of a pre-planned interim analysis (N=475). There was superior efficacy with the trastuzumab plus capecitabine combination in terms of progression-free survival (PFS) and overall survival (OS) compared to the lapatinib plus capecitabine combination. Median PFS was 6.60 months in the lapatinib-containing arm compared with 8.05 months in the trastuzumab-containing arm (HR=1.30; 95%CI 1.04 to 1.64). The median OS was 22.7 months in the lapatinib-containing arm compared with 27.3 months in the trastuzumab-containing arm (HR=1.34 (95%CI 0.95 to 1.90).

COMPLETE is a randomised Phase III study (EGF108919) (N=636) comparing the activity of lapatinib plus taxane followed by lapatinib alone versus trastuzumab plus taxane followed by trastuzumab alone as first line therapy for women with HER2 positive metastatic breast cancer. The study was stopped early due to superior efficacy of the trastuzumab plus taxane combination in terms of progression-free survival. Results from a pre-planned interim analysis showed that the PFS in the lapatinib-containing arm was lower than in the trastuzumab-containing arm (median PFS was 8.8 months in the lapatinib-containing arm compared with 11.4 months in the trastuzumab-containing arm; HR=1.33; 95% CI 1.06 to 1.67, p=0.01). The hazard ratio for OS was 1.1 (95% CI 0.75 to 1.61; p=0.62), based on 18% (n=115) deaths."

Exerpt:"The problem (using google to search for rare diseases), of course, is that common-or-garden search engines are not optimised for this process. Google, for example, considers pages important if they are linked to by other important pages, the basis of its famous PageRank algorithm. However, rare diseases by definition are unlikely to have a high profile on the web. What’s more, searches are likely to be plagued with returns from all sorts of irrelevant sources.Although still a research project, Dragusin and co have made their rare disease search engine publicly available at www.findzebra.com. This could clearly become a valuable tool for the medical community.What is less clear, however, is how this tool will be used by the general public. The site comes with the forlorn message: “Warning! FindZebra is a research project and it is to be used only by medical professionals” ."Read the full article here.

Journal of Clinical Oncology Current Issue

The Lancet Oncology

European Journal of Cancer - Articles in Press

Journal of Oncology Pharmacy Practice current issue

About Onco-PRN

Welcome and thanks for visiting Onco-P.R.N. - The oncology website with a focus on all things oncology pharmacy/pain/palliative care-related. It is intended to be an information resource for those pharmacist and relevant health care professionals involved in whatever fashion with cancer and palliative care. Stay tuned for the latest and greatest links and information with respect to: oncology medications, continuing education, pharmaceutical care initiatives, pain and symptom control, supportive care topics, and whatever else that might fit into the theme.

*Note: This website is not affiliated with Alberta Health Services (AHS) or CAPhO and the opinions expressed herewithin are that of the author(s).

Pharmacy History

"The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.[3]

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article."

Journal of Palliative Medicine - Table of Contents

Traditional Romanian Pharmacy

The Sibiu Pharmacy Museum in Sibiu, Transylvania, Romania, is housed in a 1569 Gothic townhouse where the oldest pharmacy in Romania operated for over 150 years. The pharmacy was known as La Ursul Negru (The Black Bear).

Sir William Osler: "It is much more important to know what sort of a person has a disease than what sort of disease a patient has."

William Osler is regarded as McGill’s most eminent medical graduate and, as Professor of the Institutes of Medicine, the most eminent member of the McGill Medical Faculty. At the time of his death (1919), he was without question the best known and best loved physician in the English-speaking world.